Prognostic potential of hepatic miR-122 measurements and antisense strategies targeting miR-122 as a therapeutic approach in viral hepatitis

Prognostic potential of hepatic miR-122 measurements and antisense strategies targeting miR-122 as a therapeutic approach in viral hepatitis MicroRNAs (miRNAs) are receiving attention from many clinician scientists because of numerous reports on their dysregulation in human diseases and their potential as therapeutic targets.For hepatologists, the biological function and dysregulation of hepatic miRNAs, especially the highly abundant liver-specific miR-122, is of particular interest.MiR-122 is a factor implicated in liver diseases including hepatocellular carcinoma (HCC) and chronic hepatitis C (CHC).In the context of viral hepatitis, the involvement of small non-coding RNAs in innate immune responses and virus-host interactions is of particular relevance.When discussing small 21-to 23-nucleotides (nt)-long non-coding RNAs, miRNAs have to be distinguished from small interfering RNAs (siRNAs) that are processed from long double-stranded RNAs (dsRNAs) and mediate sequence-specific gene silencing in a process referred to as RNA interference.Post-transcriptional silencing of gene expression by siRNAs is known since the late 1990s to be part of the antiviral defence in plants (1).However, more recently, small RNAs of both the siRNA and the miRNA class were also shown to function in antiviral immunity in animals, including mammals (1-3).The biogenesis of miRNAs begins with the generation of primary transcripts (termed pri-miRNAs), which, similar to protein-coding mRNAs, are synthesized by RNA polymerase II.Pri-miRNAs are processed to mi-RNAs in two consecutive steps, catalysed by RNAses Drosha [generating precursor (pre)-miRNAs] and Dicer (generating mature 21-23 nt-long miRNAs).Mature miRNAs in association with various proteins form the RNA-induced silencing complex and inhibit protein synthesis through base pairing with 3 0 -untranslated regions (UTRs) of target mRNAs (4, 5).More than 50% of all human mRNAs are predicted to be miRNA targets, and one miRNA can silence hundreds of different target mRNAs (6).Because of these features, miRNA-induced changes in gene expression can occur fast, and small changes in their levels can modulate the expression of a large number of target mRNAs.Individual miRNAs vary substantially in their expression levels, and many miRNAs are expressed in a tissue-or developmental stage-specific manner.MiR-122 belongs to the most abundant known tissue-specific miRNAs, being expressed almost exclusively in hepatocytes at over 50 000 copies per cell.This abundance allows the regulation of many different cellular processes.For instance, miR-122 is